Isoprene itself does not undergo the building process, but rather activated forms, isopentenyl pyrophosphate (IPP or also isopentenyl diphosphate) and dimethylallyl pyrophosphate (DMAPP or also dimethylallyl diphosphate), are the components in the biosynthetic pathway. IPP is formed from acetyl-CoA via the intermediacy of mevalonic acid in the HMG-CoA reductase pathway . An alternative, totally unrelated biosynthesis pathway of IPP is known in some bacterial groups and the plastids of plants, the so-called MEP(2-Methyl-D-erythritol-4-phosphate)-pathway, which is initiated from C5-sugars. In both pathways, IPP is isomerized to DMAPP by the enzyme isopentenyl pyrophosphate isomerase.
Pyruvate and glyceraldehyde 3-phosphate are converted by DOXP synthase (Dxs) to 1-deoxy-D-xylulose 5-phosphate, and by DOXP reductase (Dxr, IspC) to 2- C -methyl-D-erythritol 4-phosphate (MEP). The subsequent three reaction steps catalyzed by 4-diphosphocytidyl-2- C -methyl-D-erythritol synthase (YgbP, IspD), 4-diphosphocytidyl-2- C -methyl-D-erythritol kinase (YchB, IspE), and 2- C -methyl-D-erythritol 2,4-cyclodiphosphate synthase (YgbB, IspF) mediate the formation of 2- C -methyl-D-erythritol 2,4-cyclopyrophosphate (MEcPP). Finally, MEcPP is converted to ( E )-4-hydroxy-3-methyl-but-2-enyl pyrophosphate ( HMB-PP ) by HMB-PP synthase (GcpE, IspG), and HMB-PP is converted to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH).
The MEP pathway starts with the condensation of pyruvate and D-glyceraldehyde-3-phosphate to 1-deoxy-D-xylulose-5-phosphate (DXP or DOXP). The key isomers DMAPP and IPP are subsequently formed via a series of enzymatic steps starting with the conversion of DXP to 2C-methyl-D-erythritol-4-phosphate (MEP). Enzymes of this MEP pathway are attractive targets for the development of drugs targeting infectious diseases such as malaria and tuberculosis, because this pathway occurs in pathogenic prokaryotes but is absent in human metabolic pathways.